ADVANCED DELIVERY DEVICES - Innovation Without Change: What is it & What Can it Mean for Pharmaceutical Manufacturers?

INNOVATION IN SYRINGES
& SAFETY DEVICES

The medical hypodermic syringe with a needle was firstdeveloped in 1853 by Charles Pravaz and
Alexander Wood.The first
glass syringe with an interchangeable barrel andplunger
came from the Chance brothers in 1946, and the firstplastic
disposable hypodermic syringe came from RoehrProducts
in 1955. A year later, pharmacist Colin Murdoch wasgranted
patents for a disposable plastic syringe similar to theone we know today, and Becton Dickinson
followed with thePlastipack
in 1961.1 Since then, the pharmaceutical industryhas
burgeoned in the treatment of diseases and symptoms,leading
to novel delivery devices and safety standardsaddressing
products and production.2

The spread of infectious diseases through contaminatedneedles and needle reuse led to the
Needlestick Safety andPrevention
Act of 2000. First attempts at compliance matedexisting
syringes with “add-on” safety devices, such as shields,sheaths, and levers. A second generation
employed manualretraction
of the needle into the syringe body. These “active”devices
require two hands and are often not engaged for fearof lost
time or a needlestick; roughly 48% of sharps injuriesoccur despite the availability of sharps
protection features.3 Asa result,
needlestick injury rates have not declined asexpected.4

A third generation of “passive” devices emerged, wherebythe safety mechanism automatically engages
after the injection.These
products address previous issues but have drawbacks.Most add
an exterior structure to the syringe, which can beobtrusive,
cause anxiety, and impair visual inspection of thesyringe
contents. Due to the potential for premature activationof the safety mechanism, these designs often
require userretraining
or are incompatible with conventional techniques,such as
purging air bubbles, performing aspiration, orreconstituting
powders. Other passive products requiresignificant
changes to the drug’s primary package.

WHAT IS INNOVATION
WITHOUT CHANGE?

While these developments have moved the care of patients forward,
innovation has not been fast enough. Due to inertia caused by the development
and regulatory effort required to launch new drug delivery technologies,
advances in delivery systems are too often kept out of the market. Drug
companies have historically been forced to choose from a series of less-than-ideal
options, either choosing to do nothing, choosing to implement advances and live
with the long development path that usually comes with it, or choosing to seek
a middle ground that includes a minimalistic approach to needlestick safety but
misses the opportunity to differentiate. Because of the economic realities and
supply chain risk that must logically be considered, the crucial question is“What’s in it for the pharmaceuticalmanufacturer to embark on such achange?” Too often, the answer hasbeen “Not enough.”

Innovation
Without ChangeTM is aproduct
design and business partneringphilosophy that
shifts the paradigm sothat drug companies no
longer have to make
a bad compromise between the advances that innovation offers and the time,
cost, and risk associated with those innovations. By offering the innovation of
the final device without the traditional changes that require substantial development,
regulatory effort, and supply chain risk, Innovation WithoutChange addresses
both the end user performing the injection and the path to commercialization
for the pharmaceutical manufacturer. The Credence Companion Safety Syringe
System was born from this core philosophy. Innovation Without Change incorporates
a modular approach to the device design, leaving the primary package unchanged.
This basic tenet has the dramatic impact of simplifying the commercialization
path, reducing supply chain risk, and providing manufacturers enhanced
flexibility to respond to market changes. Drug manufacturers have complete
freedom to choose the critical primary package components from any vendor(s)
they choose. They select the syringe, plunger/stopper, and tip cap components
that are ideally suited for a specific drug, and the filling process is completely
unaffected. The Companion plunger rod and Flex Finger Flange are added to the
syringe in the common secondary assembly process; the needle is either included
in the kit in the luer presentation or already affixed to the syringe in the
staked presentation (See Figure 1).

​

While
the Companion takes the novel modular approach of building integrated safety
into an existing primary drug container, the concept of modularity is not new to
the industry. Modularity has been available in the design of the primary package
for years, with choices including the selection of syringe/drug container,
lubrication, needle size/type, stopper, tip cap/needle shield, finger flange,
and plunger rod.5,6 InnovationWithout Change builds on this
modular concept by providing the delivery device with flexibility in the
features selected. The result is an innovative device that provides marketable
differentiation, life cycle management options, product line flexibility, and
full compliance to safety legislation, all without changing the primary
package. The Companion offers the best in anti-needlestick technology,
fulfilling OSHA’s recommendations for needled device compliance. It has fully
integrated passive safety features, provides audible, tactile, and visual cues,
allows single-handed operation with the user’s hand remaining behind the
needle, and is automatically disabled after use (See Figure 2). It is designed
to be familiar to the end user, allowing routine
manipulations of the plunger rodfor air
bubble removal, aspiration, andreconstitution
techniques, full visibility ofthe barrel and
drug product, and comfortin employing all
common hand positions.But what else can Innovation
WithoutChange mean for our pharma partners,patients, and caregivers?

​

INNOVATION WITHOUT
CHANGE SHORTENS THE PATH TO COMMERCIALIZATION

Changing a drug’s primary packagecan cost
several million dollars andextend
from 6 to beyond 36 months.7 Thevalidation
work includes container closureintegrity,
sterility, biocompatibility, stability,extractables/leachables
analysis, reformulation, etc. The effects on the safety and efficacy of the
drug must be assessed via an understanding of the impact on the molecule’s
strength, quality,identity, purity, and potency.8,9 This change is designated by FDA
as requiring Prior Approval before implementation and can necessitate changes
to the filling line and manufacturing facility. Maintaining the existing
primary package simplifies the path extensively, eliminating costly and timely
variables that add risk along the way.

INNOVATION WITHOUTCHANGE DE-RISKS THESUPPLY
CHAIN

The industry and its consumers have benefitted from advances in
the critical primary package components by leading suppliers that have the
required expertise and capacity to provide reliable supply. Credence embraces
this expertise by building the Companion with the versatility to work within
the tolerances of these existing components. This provides pharma manufacturers
the flexibility to choose their preferred components and multi-source from
their preferred vendors. But Innovation Without Change extends from the
product’s design to Credence’s partnering business model and the supply chain flexibility
it provides. Just as the Companion allows a drug company to avoid changing from
its preferred package, Credence’s partnering approach allows a drug company tomaintain important supplier relationships with its molding and
assembly partners. This extends the multi-sourcing option to components of the
Companion andcapitalizes on the existing effective relationships with preferred
vendors, thereby further reducing the risk of supply chain interruption.

For example, different userpopulations have different devicepreferences.
A small study shows userpreference
for a prefilled syringecompared to
an auto injector rangingfrom 33% to
67%, depending on thedisease state.10
The ability to direct asterile
filled drug container into an autoinjector or into a differentiatedneedlestick prevention safety syringegives a drug company efficient
flexibility(See Figure 3).
Similarly, thoughdeveloping nations
have different economic realities than developedmarkets, they have a great need forneedlestick prevention and syringedisabling technology. Once again, themodularity of the Companion provides aviable solution. By changing the plungerrod, a drug company can provide moreviable markets with passive needleretraction, while providing developingmarkets with active retraction. The drugcompany gains the flexibility to provideneedlestick safety and single usetechnology to both markets whiledifferentiating the cost of goods. Further,as needlestick prevention legislationexpands to new geographies and newpoints of care (the home?), the ability togain compliance and a market edge bybuilding off of the existing drug containerbecomes critical. Prior to InnovationWithout Change, this flexibility was muchmore difficult to attain.

Human factors improvements are often left behind when delivery
system innovations don’t make it to market, despite the fact that they can promote
more accurate dosing and more efficient healthcare. By simplifying the commercialization
path, the Companion facilitates getting important improvements into patient and
caregiver hands. For example, the Companion’s user has full visibility of the
syringe barrel and drug product and can perform standard air bubble removal and
aspiration techniques without fear of prematurely engaging the safety
mechanism. Further, the flexibility of Innovation WithoutChange allows
customization of the thumb pad and finger flange, whether the goal is to
maximize user comfort or minimize footprint.

Needles represent another area of human factors focus. Long
needles, such as those used for intramuscular injections, have been largely
ignored by safety technology suppliers due to the challenge of passively
protecting them, yet, these long needles may be the most dangerous. Perhaps due
to the lack of adequate safety, long needles are not being used when they ought
to be. Of the medications with an intramuscular route of administration, it is
estimated that few women and about 15% of men actually receive the drug in the intramuscular
space because the needle being used is not long enough.11 This is an area where
a luer needle can have a major impact; the Companion’s luer solution allows the
right needle to be selected for the specific patient, and it also provides
passive needle retraction for any practical needle length. But traditionally,
luer needles have been susceptible to improper connections between the needle
and the syringe, resulting in complaints of spilled drug product, inaccurate
dosing, and needles left behind in patients. To address this, the Companion
Guide-On Needle Cover provides the user visual, audible, and tactile cues of a
successfully connected needle. Further, the cover cannot be removed from the
needle until the user has twisted the needle on properly to a designated torque
level. Therefore, the user is prevented from attempting an injection with an
improperly connected needle (See Figure 4).

​

This is extremely important in reconstitution applications where
luer needles are required to provide a sharp needle for injection into the
patient. The Guide-On Needle Cover helps ensure the needle is attached
properly. Of further importance, the Companion can be used without fear of
premature safety activation during the diluent delivery and subsequent drawing
up of the reconstituted solution. These manipulations of the plunger rod often cause
conventional safety devices to prematurely activate. The Companion allows conventional
reconstitution with passive needlestick safety (See Figure 5). Should the
manufacturer wish to pursue a dual-chamber presentation, Credence’s Innovation
Without Change approach can also apply.

​

It allows the pharmaceutical manufacturer the freedom to choose
the desired reconstitution approach while still employing the best in
needlestick safety. If the pharmaceutical manufacturer wishes to employ a
staked needle because neither needle choice flexibility nor reconstitution is
needed, the Innovation Without Change design philosophy can also allow
this choice. The user experiences the same passive needle safety and human
factors benefits but does not have to attach a needle. The manufacturer can
still choose its desired syringe, stopper, and needle shield primary package
components, just as is done with the luer solution, and the filling process
remains unchanged. Further, because adhesive is not present in the Companion
system, a risk of undesirable interaction with the drug substance is removed.

INNOVATION WITHOUTCHANGE EMPOWERS BRANDMANAGEMENT

Innovation Without Change providesinnovator companies a means ofextending the life cycle of theircommercial
drugs by enhancing safetyand
usability, thus placing meaningfulbarriers
to competitive threats fromgeneric
follow-ons. This strategy can alsobe
employed to differentiate follow-onmolecules
from the innovator and hasparticular
value for biosimilars. TheFDA’s
Proposed Guidance for Industry onBiosimilars
allows for the potential use ofdelivery
systems that are differentiatedfrom
those of the innovator product.12Biosimilar
manufacturers can thereforecapitalize
on recent advances in deliverysystems
and also differentiate onsomething
tangible other than price. Sowhether
it is the innovator providingbarriers
to the follow-on, or the follow-ondifferentiating
from the innovator, thedelivery
device becomes a meaningfuland
valuable tool; Innovation WithoutChange allows the differentiation tooccur without the development pathcomplexity and sourcing risk traditionallyassociated with the effort.

The modular approach also makes iteasier for engineers and marketers totailor the device specifically for the drug,user population, or brand. For example,specified colors or logos can be used, orthe finger flange and thumb pad can be fashioned to provide a more robust interface. But Innovation
Without Change can do something more revolutionary. As the trend toward
home administration of injectable medications continues, home injectors will
seek the kind of individual customization that is more typical in products from
technology and consumer goods industries. Just as consumers select different
covers and colors for theiriPhones or will change backgrounds for their Apple Watches, what
if consumer injectors could customize their safety injection device with à la
carte component choices? Innovation WithoutChange provides the
modularity needed for devices to be customized and built for individual tastes
and preferences. When the modularity of the device converges with regulatory
strategy vision and supply chain flexibility, the possibilities exist for the
expression of “personalized medicine” in injection devices.

SUMMARY

A rigorous, risky development andregulatory process forces pharmaceuticalmanufacturers into a bad compromisebetween advances in delivery systemsand the time, cost, and risk associatedwith those advances. Often, the choice isto forsake the advances, even if theexpected benefits can include life-saving safety improvements and human factors enhancements that lead to
safer, more efficient, and more effective healthcare. Innovation Without
Change shifts the paradigm and affords drug manufacturers the flexibility
they have not previously had. The Credence Companion Safety Syringe System,
built around the foundation of an existing drug container and components,
allows a modular “pick-and-choose” approach to the design of the delivery
device. By minimizing the cost, time, and risk of commercializing their drugs
with the Companion System, pharmaceutical manufacturers can incorporate the differentiating
safety and usability features that their users need, that legislation requires,
and that customers increasingly mandate.

John A. Merhige is Chief Commercial Officer at
Credence MedSystems, leading the company’s business development, sales, and
marketing strategies. Previously, John was Vice President, Market Development
at Sanofi BioSurgery. He joined Sanofi upon its acquisition of Pluromed, which
he joined in its early stages and was a member of the executive management
team. Previously, Mr. Merhige founded Prelude Devices to identify early stage
medical device ventures and gained general management and commercial leadership
experience at Ford and Avery Dennison. He graduated from Dartmouth College with
a Mechanical Engineering degree and returned to Dartmouth for a Masters in
Engineering Management from the Thayer School of Engineering and the Tuck
School of Business. He is a member of MassMEDIC, MassBio, and has served on the
Board of Directors of the MedDev Group (MDG).

Dan Thayer is Technology Director of Credence
MedSystems, where he uses his deep industry knowledge to further the company’s
product development and intellectual property efforts. He is a successful entrepreneur
and skilled problem solver. His experience includes ventures in the hospitality
and auto industries; in the latter he performed as a racing and test driver for
Toyota USA, GM, Mercedes, BMW, Anson, and Tiga race cars. More recently, Mr.
Thayer has been focused on needlestick safety technology. His efforts have led
to several technological breakthroughs designed to protect healthcare workers
and patients.